title: Isoquercetin protects cortical neurons from oxygen-glucose deprivation-reperfusion induced injury via suppression of TLR4-NF-кB signal pathway.
abstract: In the present study, oxygen-glucose deprivation followed by reperfusion (OGD/R), an in vitro model of ischemia, was used to evaluate the neuroprotective effect of isoquercetin in primary culture of rat cortical neuronal cells. It was found that isoquercetin administered prior to the insult could prevent OGD/R-induced intracellular calcium concentrations ([Ca(2+)]i) increase, lactate dehydrogenase (LDH) release and cell viability decrease. For the first time, isoquercetin is described as a neuroprotective agent that potentially explains the alleviation and prevention from OGD/R-induced injury in neurons. Mechanistic studies showed that the neuroprotective effect of isoquercetin was carried out by anti-inflammatory signaling pathway of inhibiting protein expression of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB), and mRNA expression of TNF-α and IL-6, accompanied by the anti-apoptotic signaling pathway of deactivation of extracellular-regulated kinase (ERK), Jun kinase (JNK) and p38, and inhibition of activity of caspase-3. Therefore, these studies highlighted the confirmation of isoquercetin, a flavonoid compound, as an anti-inflammation and anti-apoptosis factor which might be used as a therapeutic strategy for the ischemia/reperfusion (I/R) brain injury and related diseases.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Li
authors.forename: Lu-Zhong
authors.initials: LZ
authors.lastname: Zhang
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Zhang
authors.forename: Shu
authors.initials: S
authors.lastname: Yu
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Liang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D005947:Glucose / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D011794:Quercetin; D005947:Glucose; D010100:Oxygen
keywords: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Apoptosis; DMEM; Dulbecco’s Modified Eagle’s Medium; ERK; FBS; I/R; Inflammation; Ischemia; Isoquercetin; JNK; Jun kinase; LDH; MAP; MCAO; MTT; NF-κB; OGD/R; Oxygen–glucose deprivation followed by reperfusion (OGD/R); PI; RT-PCR; Reverse Transcription-Polymerase Chain Reaction; SD; Sprague–Dawley; TLR4; TLRs; [Ca(2+)](i); extracellular-regulated kinase; fetal bovine serum; intracellular calcium concentrations; ischemia/reperfusion; lactate dehydrogenase; middle cerebral artery occlusion; mitogen-activated protein; nuclear factor-kappa B; oxygen–glucose deprivation followed by reperfusion; propidium iodide; toll-like receptor 4; toll-like receptors